Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.17.21 (prostate-specific membrane antigen)
 1,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Radical prostatectomy is one treatment for organ-confined prostatic adenocarcinoma. Dissemination of malignant prostatic cells after radical prostatectomy could be partly due to prostate manipulation during dissection. We confirmed by assay of prostate-specific membrane antigen by reverse-transcription nested PCR that prostate manipulation seeded prostatic epithelial cells in the general circulation in 12 of 14 consecutive patients operated on for organ-confined prostate adenocarcinoma. Our results suggest that surgeons should approach radical prostatectomy with care to avoid seeding from the prostate gland. Antiandrogen therapy might reduce the haematogenous spread of prostatic cells during radical prostatectomy.
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PMID:Haematogenous dissemination of prostatic epithelial cells during radical prostatectomy. 862 40

We report the development of a new sensitive nested reverse transcription-polymerase chain reaction (RT-PCR) assay, using primers derived from the prostate-specific membrane antigen (PSM) cDNA sequence, to detect an hematogenous spread of prostate adenocarcinoma cells. In 60 patients with a biopsy-proven prostate cancer, PSM and PSA RT-PCR detected circulating prostate cells in 40 and 20 patients, respectively. In pT4 M+ and pT3 M+ disease patients, nested PSM primers detected cells in 28 of 33 patients (85%), whereas nested PSA primers detected cells in 17 of 33 (51%). In patients with organ-confined cancer spread (pT2a and pT2b patients) before radical prostatectomy, nested PSM RT-PCR detected circulating prostatic epithelial cells in 6 of 17 patients (35%), which suggests that an hematogenous spread of prostate cells may occur early in prostate cancer history. Altogether, these results suggest that the detection of PSM-expressing cells in blood may predict the development of cancer in patients without clinically apparent prostate cancer. Nevertheless, the potential application and the clinical significance of detection of hematogenous prostate cells through the use of nested PSM primers need an extensive longitudinal study.
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PMID:Enhanced detection of hematogenous circulating prostatic cells in patients with prostate adenocarcinoma by using nested reverse transcription polymerase chain reaction assay based on prostate-specific membrane antigen. 749 5

We have recently cloned a 2.65-kilobase complementary DNA (cDNA) encoding the prostate-specific membrane antigen (PSM) recognized by the 7E11-C5.3 anti-prostate monoclonal antibody. Immunohistochemical analysis of the LNCaP, DU-145, and PC-3 prostate cancer cell lines for PSM expression using the 7E11-C5.3 antibody reveals intense staining in the LNCaP cells with no detectable expression in both the DU-145 and PC-3 cells. Coupled in vitro transcription/translation of the 2.65-kilobase full-length PSM cDNA yields an M(r) 84,000 protein corresponding to the predicted polypeptide molecular weight of PSM. Posttranslational modification of this protein with pancreatic canine microsomes yields the expected M(r) 100,000 PSM antigen. Following transfection of PC-3 cells with the full-length PSM cDNA in a eukaryotic expression vector, we detect expression of the PSM glycoprotein by Western analysis using the 7E11-C5.3 monoclonal antibody. Ribonuclease protection analysis demonstrates that the expression of PSM mRNA is almost entirely prostate specific in human tissues. PSM expression appears to be highest in hormone-deprived states and is hormonally modulated by steroids, with 5-alpha-dihydrotestosterone down-regulating PSM expression in the human prostate cancer cell line LNCaP by 8-10-fold, testosterone down-regulating PSM by 3-4-fold, and corticosteroids showing no significant effect. Normal and malignant prostatic tissues consistently show high PSM expression, whereas we have noted heterogeneous, and at times absent, expression of PSM in benign prostatic hyperplasia. LNCaP tumors implanted and grown both orthotopically and s.c. in nude mice abundantly express PSM, providing an excellent in vivo model system to study the regulation and modulation of PSM expression.
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PMID:Expression of the prostate-specific membrane antigen. 751 Oct 53

A highly sensitive nested reverse transcriptase-PCR assay, with primers derived from the prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSM) cDNA sequences, has been used to detect occult hematogenous micrometastatic prostate cells. In 77 patients with prostate cancer, PSM and PSA primers detected circulating prostate cells in 48 (62.3%) and 7 (9.1%) patients, respectively. In treated stage D disease patients, PSM primers detected cells in 16 of 24 patients (66.7%), while PSA primers detected cells in 6 of 24 (25%). In post-radical prostectomy patients with negative serum PSA values, PSM primers detected metastases in 21 of 31 patients (67.7%), whereas PSA primers detected cells in only 1 of 33 (3.0%), indicating that micrometastatic spread may be a relatively early event in prostate cancer. The analysis of 40 individuals without known prostate cancer provides evidence that this assay is highly specific and suggests that PSM expression may predict the development of cancer in patients without clinically apparent prostate cancer. Using PSM primers, we detected micrometastases in 4 of 40 controls, 2 of whom had known benign prostatic hyperplasia and were later found to have previously undetected prostate cancer. The clinical significance of detection of hematogenous micrometastic prostate cells using PSM primers and potential applications of this molecular assay, as well as the assay for PSA, merit further study.
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PMID:Sensitive nested reverse transcription polymerase chain reaction detection of circulating prostatic tumor cells: comparison of prostate-specific membrane antigen and prostate-specific antigen-based assays. 752 94

Previous studies have suggested that serum prostate-specific antigen (PSA) levels are under androgenic influence, especially in patients with adenocarcinoma of the prostate. PSMA (prostate-specific membrane antigen) is thought to reflect hormonal or clonal resistance or an independence with respect to testosterone regulation. The influence of testosterone on serum PSA expression in normal men is not clear. We studied the effect of exogenous testosterone administration on the serum levels of PSA and PSMA in hypogonadal men. Serial serum PSA, serum PSMA by Western blot, and serum total testosterone levels were obtained at intervals of every 2-4 weeks in 10 hypogonadal men undergoing treatment with exogenous testosterone, delivered as testosterone enanthate injection or by testosterone patch. Linear and quadratic orthogonal polynomial scores were calculated for PSMA, PSA, and testosterone. A 2-tailed, paired t-test failed to demonstrate a significant correlation between serum PSA (linear P = 0.432, quadratic P = 0.290) or PSMA (linear P = 0.162, quadratic P = 0.973) and serum testosterone levels. This study suggests that in hypogonadal men, neither PSMA nor PSA expression is testosterone-dependent.
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PMID:Effect of exogenous testosterone replacement on prostate-specific antigen and prostate-specific membrane antigen levels in hypogonadal men. 754 73

The prostate-specific membrane antigen (PSMA) glycoprotein is recognized by the monoclonal antibody (MAb) 7E11-C5.3 as a predominant 100 kDa and minor 180 kDa component in LNCaP cell line extracts and its expression has been shown by immunohistochemistry to be highly restricted to prostate epithelium. The aim of the present study was to utilize Western blot analysis to determine if PSMA could be detected in human tissue extracts and body fluids and if so, which molecular forms were present. PSMA was detected as 120 and 200 kDa bands in normal, benign and malignant prostate tissues and seminal plasma. Further analysis demonstrated that the larger molecular form of PSMA may be a dimer of the lower m.w. species. The PSMA glycoprotein was not detected in the majority of non-prostate tissue extracts examined except for a low yet significant amount in normal salivary gland, brain and small intestine, suggesting that PSMA may not be as prostate-specific as originally thought. Since the prostate-specific antigen (PSA) has been shown to be maximally shed into the serum in high-grade and metastatic prostate carcinomas, it was surprising that PSMA could not be detected in serum by Western blot analysis even in patients with actively progressive metastatic disease. Second generation antibodies generated against different epitopes may be required to determine if PSMA is shed into serum. Our results support the hypothesis that PSMA is a novel prostate biomarker.
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PMID:Detection and characterization of the prostate-specific membrane antigen (PSMA) in tissue extracts and body fluids. 766 26

We examined expression of prostate-specific membrane antigen (PSM) mRNA in normal prostate using reverse transcription-PCR and sequencing. An alternatively spliced variant, PSM', along with the previously described PSM form, was found in normal prostate. PSM' cDNA is shorter (2387 nucleotides) than PSM (2653 nucleotides). The cDNAs are identical except for a 266-nucleotide region near the 5' end of PSM cDNA (nucleotide 114-380) that is absent from PSM'. This deleted region includes the translation initiation codon and codons for the putative transmembrane domain of PSM. Thus, PSM' RNA codes for a protein that has no apparent signal sequence. We verified the existence of spliced mRNA variants in human primary tissue specimens by RNase protection assay. In LNCaP human prostatic cancer cells and in primary prostate tumors, PSM is the dominant form. In contrast, normal human prostate expressed more PSM' than PSM. Benign prostatic hypertrophy samples showed about equal expression of both variants. We quantified the relative expression of each variant by densitometry and compiled a tumor index, which is the ratio of PSM:PSM' level. LNCaP has an index ranging from 9-11, carcinoma of the prostate from 3-6, benign prostatic hypertrophy from 0.75-1.6, and normal prostate from 0.075-0.45. The index reflects the increased expression of PSM over PSM' following the progression from normal to tumor state. This tumor index may be a useful indicator for the measurement of tumor progression. PSM and PSM' may be functionally different proteins as a result of differences in structure or cellular location. We are investigating the prevalence of one form over the other and how it may influence tumor progression.
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PMID:Alternatively spliced variants of prostate-specific membrane antigen RNA: ratio of expression as a potential measurement of progression. 788 49

There is a need for the development of new diagnostic tools for the early detection of prostate cancer. A candidate molecule for a new screening test is a prostate-specific membrane antigen (PSM) recognized by the monoclonal antibody 7E11.C5. We carried out studies aimed at identifying PSM in the serum of normal and benign prostatic hyperplasia (BPH) donors and patients with adenocarcinoma of the prostate, in order to judge whether the development of a serum assay using this marker was feasible. By Western blotting, we found significant levels of PSM in serum samples from prostatic cancer patients, in the seminal fluid of pooled normal donors, in BPH patients, and in normal male sera. Similar to prostate-specific antigen (PSA), PSM was present in seminal plasma in higher concentrations than in serum, and PSM levels in prostatic cancer patients were significantly higher than in normal controls. These data suggest that the development of an assay utilizing the PSM and new monoclonal antibodies directed against the antigen, could provide a feasible test for prostatic cancers.
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PMID:Western blot assay for prostate-specific membrane antigen in serum of prostate cancer patients. 808 37

Dendritic cells (DCs) are "professional" antigen-presenting cells capable of stimulating T-cell proliferation and cytotoxicity when loaded with and presenting specific antigens, including tumor antigens. We demonstrated the stimulation of an autologous cytotoxic T-cell response elicited by DC loaded with autologous tumor cell lysate derived from primary prostate tumor. A candidate tumor antigen is prostate-specific membrane antigen (PSMA), which is overexpressed in prostate cancer patients. We identified a HLA-A2 motif in PSMA, isolated patient DC, loaded peptide into DC, and stimulated autologous T cells to proliferate. The ability to use DC for presentation of either tumor or peptide antigen in an HLA-restricted fashion in order to stimulate T-cell proliferation and cytotoxicity demonstrates the potential of this technology for development of a prostate cancer vaccine.
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PMID:Presentation of prostate tumor antigens by dendritic cells stimulates T-cell proliferation and cytotoxicity. 854 83

This report demonstrates that the investigational prostatic carcinoma marker known as the prostate-specific membrane antigen (PSM) possesses hydrolytic activity with the substrate and pharmacologic properties of the N-acetylated alpha-linked acidic dipeptidase (NAALADase). NAALADase is a membrane hydrolase that has been characterized in the mammalian nervous system on the basis of its catabolism of the neuropeptide N-acetylaspartylglutamate (NAAG) to yield glutamate and N-acetylaspartate and that has been hypothesized to influence glutamatergic signaling processes. The immunoscreening of a rat brain cDNA expression library with anti-NAALADase antisera identified a 1428-base partial cDNA that shares 86% sequence identity with 1428 bases of the human PSM cDNA [Israeli, R. S., Powell, C. T., Fair, W. R. & Heston, W.D.W. (1993) Cancer Res. 53, 227-230]. A cDNA containing the entire PSM open reading frame was subsequently isolated by reverse transcription-PCR from the PSM-positive prostate carcinoma cell line LNCaP. Transient transfection of this cDNA into two NAALADase-negative cell lines conferred NAAG-hydrolyzing activity that was inhibited by the NAALADase inhibitors quisqualic acid and beta-NAAG. Thus we demonstrate a PSM-encoded function and identify a NAALADase-encoding cDNA. Northern analyses identify at least six transcripts that are variably expressed in NAALADase-positive but not in NAALADase-negative rat tissues and human cell lines; therefore, PSM and/or related molecular species appear to account for NAAG hydrolysis in the nervous system. These results also raise questions about the role of PSM in both normal and pathologic prostate epithelial-cell function.
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PMID:Prostate-specific membrane antigen is a hydrolase with substrate and pharmacologic characteristics of a neuropeptidase. 857 Jun 28


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